Kaposi's Sarcmoa

KS is a AIDS defining illness with a course ranging from indolent, with only skin manifestations to fulminant, with extensive visceral involvement.

1. Kaposi’s Sarcoma

2. Kaposi sarcoma was first described as ‘idiopathic multiple pigmented sarcoma of the skin’ by the Hungarian dermatologist Moritz Kaposi in 1872.

3. From that time until the HIV disease epidemic identified with AIDS, KS remained a rare tumor. It became more widely known as one of the AIDS-defining illnesses in the 1980s.

4. Causative agent KSHV was discovered as a causative agent in 1994. Kaposi sarcoma (KS) is a multifocal, endothelial proliferation caused by human herpesvirus 8 (HHV‐8) The disease is multifocal, with a course ranging from indolent, with only skin manifestations to fulminant, with extensive visceral involvement.

5. Although HHV‐8 is considered the causative agent, it is insufficient to cause KS alone. Multiple co‐factors are required, the most powerful of which is HIV co‐infection, which elevates the risk up to 20,000‐fold.

6. There are four distinct clinicopathological subtypes: ➤ Classic (Sporadic KS) ➤ Endemic (sub-Saharan Africa) ➤ Iatrogenic (transplant recipients) ➤ AIDS associated (Epidemic KS)

7. KS in MSM with­out HIV infection is increasingly being recognized as a possible distinct fifth form of KS

8. Incidence varies dramatically from less than 1 per 100,000 in western Europe and North America to over 22 per 100,000 in central Africa where the disease occurs in its endemic form and HIV infection is rampant.

9. Classic KS occurs mostly in elderly men of Mediterranean or Jewish ancestry 10-15 times more common in men than women. Chronic lymphedema is a frequent association. Classic KS

10. It typically shows an indolent, protracted clinical course and primarily affects skin on the legs, though lymph nodes & visceral mucosa may also be involved. Slow progression with good prognosis. Occasionally an aggressive type of Kaposi’s sarcoma occurred in young adults or children with early lymph node involvement.

11. African / Endemic KS Presents in young adults median age 37. Males > Females Accounts for up to 9% of all reported cancers in equatorial Africa. Poor prognosis

12. In South Africa, it has been estimated that Kaposi’s sarcoma is ten times more common in blacks than whites. In Africans, the disease can run a similar course as in Classic KS, but a higher proportion of young people are affected, with a more aggressive disease manifestation .

13. Most cases in children, with or without HIV infection, are of the lymphadenopathic type and are rapidly fatal due to visceral dissemination .

14. 4 clinical patterns Nodular type : benign course & resembles classic KS. Florid / Vegetating type : More aggressive, extend deeply into the subcutis, muscle & bone. Infiltrative type : More aggressive. Has mucocutaneous & visceral involvement. Lymphadenopathic type : Seen in children (male:female = 3:1) & young adults. Viscera & massive LN involvement. Early death.

15. Fungating lesions seen in Florid / Vegetating type of KS

16. Iatrogenic KS Most common in solid organ transplant recipients. Chronic use of immunosupressive drugs. Cyclosporine is associated with a higher incidence and more rapid onset of disease. Resolves on cessation of immunosupression.

17. Incidence of KS is reported to currently be ~200- fold higher in recipients of solid-organ transplants (that is, in iatrogenic KS) than in the general population No sex predilection.

18. HIV associated KS Risk 20,000 times more in AIDS patient compared to general population. Common in homosexual men. Visceral involvement may be present without any skin lesions

19. Rapid progression, atypical distribution affecting the trunk & extensive systemic involvement in HIV.

20. Disseminated AIDS-related KS in a 36-year-old man. Nodular violaceous involvement of the tongue base & soft and hard palates.

21. Multifocal involvement of respiratory system can be asymptomatic or lead to dyspnea, cough, hemoptysis and/or chest pain. GI complications include ulceration, massive haemorrhage , perforation and ileus. Small intestine is the most common location.

22. KS of bowel and/or lungs is responsible for numerous deaths. HIV-associated KS is an aggressive tumor that results in a median survival time of 18 months without treatment.

23. Diagnosis Dermoscopy - Dermoscopic examination reveals ➤ bluish-reddish coloration ➤ areas showing various colours of the rainbow spectrum ➤ scaly surface Skin biopsy – Vascular channels lined by atypical endothelial cells. Extravasated erythrocytes with hemosiderin deposition.

24. Immunohistochemistry – LANA-1, CD31, CD34, D2-40 positivity Imaging – Abdominal ultrasound, CXR, HRCT, (extent of visceral involvement)

25. Dermoscopic findings (non-polarized light) White lines & clods Purplish-pinkish colouration Surface scale Rainbow pattern

26. purple-white colour, polychromatic colour change , surface scale, haemorrhagic clot

27. Dermoscopic findings (polarized light) purplish-pinkish coloration rainbow pattern scaly surface small brown globules

28. bluish-reddish colouration (a, b), scaly surface (c)

29. The ‘ rainbow pattern’ in Kaposi’s sarcoma

30. The histopathological changes of KS typically parallel the clinical progression of patch, plaque and nodular stages.

31. Patch stage KS Clinical lesions consist of violaceous to brown erythematous patches and plaques, most often involving the feet in classic KS and often involving the face in AIDS‐associated KS

32. Histopathology – Patch stage Promontary sign - Normal adnexal structures and preexisting blood vessels often protrude into newly formed blood vessels

33. horizontally arranged, irregular vessels that dissect in between collagen bundles and around adnexae, vessels lined by hyperchromatic plump endothelial cells , with areas of erythrocyte extravasation & hemosiderin deposition.

34. Plaque stage KS Well defines violaceous erythematous plaques

35. In the reticular dermis- spindle cell vascular proliferation characterized by slit-like vascular spaces with extravasated erythrocytes Plaque stage

36. Plaque-stage Kaposi’s sarcoma. A more cellular dermis with extensive hemorrhage.

37. Nodular KS Clinical lesions consist of well‐demarcated, erythematous, firm nodules, often with accompanying lymphoedema.

38. Nodular stage Fairly well circumscribed dermal nodule with whorled arrangement of spindled cells.

39. Angiomatous Kaposi’s sarcoma. Congested small vascular channels in a focal sievelike pattern.

40. Lymphangiomatous Kaposi’s sarcoma. Numerous, irregular, dilated, bloodless vascular channels with a striking lymphangioma-like appearance.

41. Immunohistochemistry

42. Immunohistochemical staining - antibodies against latency-associated nuclear antigen ( LANA-1 ) demonstrates presence of HHV-8

43. The blood vessels of normal granulation tissue (top) overlying an ulcerated KS tumour (bottom) are more strongly immunoreactive for CD31 than are KS tumour cells.

44. nodular stage KS positive for CD31 is slightly less than that of patch/plaque–stage KS, suggesting that there may be subtle differences in the staining patterns for endothelial markers between the different histologic stages of KS .

45. CD34 demonstrates strong immunoreactivity in KS spindle cells. Sensitivity – AIDS related KS – 100% Non-AIDS related KS – 100%

46. D2-40 stains all KS lesional cells in this cutaneous KS nodule Sensitivity – AIDS related KS – 100% Non-AIDS related KS – 92%

47. Differential diagnosis of KS Depending on site, distribution & morphology of lesions of KS in individual cases, the D/D can vary from- Naevus Histiocytoma Cryptococcosis Histoplasmosis Leishmaniasis Pneumocystis lesions Dermatophytosis Angioma Bacillary angiomatosis Pyogenic granuloma Melanoma

48. Management (local) KS may resolve spontaneously in immunocompetent individuals. Radiotherapy Cryotherapy Laser Alitretinoin gel Photodynamic therapy

49. Surgical excision Topical antivirals: cidofovir, docosanol Intralesional, e.g. IFN‐α, TNF‐α, vinca alkaloids Surgery, e.g. cautery, infrared coagulation

50. Early‐stage KS (T0 stage): • cART • Local radiotherapy or liposomal anthracycline for rapidly progressing or cosmetically disfiguring disease Advanced‐stage KS (T1 stage): • cART & liposomal anthracycline (daunorubicin 40 mg/m² every 14 days or doxorubicin 20 mg/m² every 21 days) Anthracycline‐refractory KS: • cART & paclitaxel (100 mg/m² every 14 days) Management (generalized lesion)

51. cART Isotretinoin Cidofovir Intravenous chemotherapy, e.g. anthracyclines such as liposomal daunorubicin, liposomal doxorubicin, bleomycin, paclitaxel, vincristine, etoposide Human chorionic gonadotrophin? Interleukin 4 Imatinib mesylate (platelet‐derived growth factor/c‐kit receptor inhibitor) Thalidomide, lenalidomide, Sirolimus

52. INF- α2 b can be used in management of AIDS-associated Kaposi sarcoma. Dosing - 30 million IU/m2 subcutaneously or IM 3 times/week until disease progression or maximal response has been achieved after 16 weeks. Biologicals

53. Ethel Cesarman, Blossom Damania, Susan E. Krown, Jeffrey Martin, Mark Bower, and Denise Whitby Kaposi sarcoma Nat Rev Dis Primers. 2019 Jan 31; 5(1): 9. Rook’s textbook of dermatology 9 th edition Fitzpatrick’s Dermatology 9 th edition IADVL 5 th edition Bolognia 4 th edition https://www.cancer.gov/types/soft-tissue-sarcoma/hp/kaposi-treatment-pdq#section/all

54. Eleonora Ruocco, Vincenzo Ruocco, Maria Lina Tornesello, Alessio Gambardella, Ronni Wolf, Franco M Buonaguro Kaposi's sarcoma: etiology and pathogenesis, inducing factors, causal associations, and treatments: facts and controversies Clin Dermatol. 2013 Jul-Aug;31(4):413-422 William Kamiyango, Jimmy Villiera, Allison Silverstein, Erin Peckham-Gregory, Liane R. Campbell, and Nader Kim El-Mallawany Navigating the Heterogeneous Landscape of Pediatric Kaposi Sarcoma Cancer Metastasis Rev. 2019 Dec; 38(4): 749–758.

55. Tuğçe Ertürk Yılmaz, Bengü Nisa Akay, Aylin Okçu Heper Dermoscopic findings of Kaposi sarcoma and dermatopathological correlations Australas J Dermatol 2020 Feb;61(1):e46-e53. S-T Cheng, C-L K Ke, C-H Lee, C-S Wu, G-S Chen, S C-S Hu Rainbow pattern in Kaposi's sarcoma under polarized dermoscopy: a dermoscopic pathological study Br J Dermatol 2009 Apr;160(4):801-9. Carlos S. Restrepo, Santiago Martínez,2, Julio A. Lemos, Jorge A. Carrillo, Diego F. Lemos, Paulina Ojeda, Prakash Koshy Imaging Manifestations of Kaposi Sarcoma Radiographics. 2006 Jul-Aug;26(4):1169-85.

56. Flavia G Nunes Rosado, Doha M Itani, Cheryl M Coffin, Justin M Cates Utility of immunohistochemical staining with FLI1, D2-40, CD31, and CD34 in the diagnosis of acquired immunodeficiency syndrome-related and non-acquired immunodeficiency syndrome-related Kaposi sarcoma Arch Pathol Lab Med. 2012 Mar;136(3):301-4. L Pantanowitz, C N Otis, B J Dezube Immunohistochemistry in Kaposi's sarcoma Clin Exp Dermatol. 2010 Jan;35(1):68-72.

57. Thank You